We have recently generated a mouse strain that is deficient for the fibulin-5 gene by homologous recombination. Fibulin-5 belongs to the fibulin family of extracellular matrix proteins and is abundantly expressed in the skin, lungs, and aortas. Fibulin-5 homozygous mutant mice develop systemic elastinopathy including loose skin, emphysematous lung and tortuous and elongated aorta. Morphological studies as well as biochemical analyses revealed that fibulin-5 acts as bridging molecule between elastic fibers and the surrounding cell surface, and is essential for the final organization of elastic fibers in vivo. By utilizing fibulin-5 mutant mice, we will investigate the role of fibulin-5 in skin wound repair with respect to elastic fiber regeneration and healing. We will also explore the possibility of modulating wrinkle formation in vivo by investigating the role of fibulin-5 in physiological aging. Third, we will establish an in vitro culture system to obtain cross- linked and organized elastic fibers by establishing co-culture condition for cells over-expressing tropoelastin, fibulin-5 and cell surface integrin. These studies will provide a strong basis for a therapeutic implication for skin wound treatment and wrinkle treatment.